Showing papers on "Hypophysectomy published in 1989"

σ-Receptors in Endocrine Organs: Identification, Characterization, and Autoradiographic Localization in Rat Pituitary, Adrenal, Testis, and Ovary

Abstract: We have used a variety of selective radioligands to identify and localize sigma- and phencyclidine (PCP)-binding sites in rat endocrine organs. [3H]Haloperidol-labeled sigma-receptors were identified in membrane homogenates of rat pituitary, adrenal, testis, and ovary which had kinetic and pharmacological characteristics similar to those of the well characterized sigma-receptors in rat cerebellum. The highest density of sigma-receptors was present in the ovary, with progressively lower densities present in the testis, pituitary, adrenal, and cerebellum, respectively. In autoradiographic studies, sigma-receptors [labeled with d-3-(3-hydroxyphenyl)N-(1-propyl-2,3-[3H]piperidine or [3H]1,3-di-(2-tolyl)guanidine] were discretely localized within the endocrine tissues. In the pituitary, the highest density of sigma-receptors was found in the anterior lobe. In the adrenal, sigma-receptors were localized primarily in the cortex. In the testis, sigma-receptors were present in highest concentrations in the ductuli efferentes and ductus epididymis; lower densities of binding sites were present in the seminiferous tubules, and no binding was seen in the interstitial tissue. In the ovary, sigma-receptors were localized in high density in the maturing follicles, and lower densities were present in resting follicles. After hypophysectomy, there were relative increases in the densities of sigma receptors in the remaining tissue in the adrenal gland and testis. In contrast, hypophysectomy resulted in a marked depletion of sigma-binding sites in the ovary. The data from hypophysectomized rats indicate that the highest densities of sigma-receptors in the ovary are localized to (LH-dependent) maturing follicles, while sigma-binding sites in adrenal and testis are localized to cells that are not dependent on trophic maintenance by the pituitary. In contrast, high affinity PCP receptors were not detected in pituitary, adrenal, testis, or ovary either by homogenate binding studies with 3,4-[3H]N-[1-(2-thienyl)cyclohexyl]piperidine or in vitro autoradiography using 3,4-[3H]N-[1-(2-thienyl)cyclohexyl]piperidine and d-[3H]5-methyl-10,11-dihydro-5H-dibenzo-[a,d] + cyclohepten-5,10-imine. In summary, the data suggest that the reported endocrine effects of PCP and the prototypic sigma-receptor agonist N-allylnormetazocine are probably mediated either through direct action on sigma-receptors in the pituitary and/or target endocrine organs or by actions on sigma- and/or PCP receptors in brain.

Hypophysectomy differentially alters P-450 protein levels and enzyme activities in rat liver: pituitary control of hepatic NADPH cytochrome P-450 reductase.

Abstract: Pituitary-determined hormones regulate the expression of hepatic cytochromes P-450 through processes involving both negative and positive controls. Accordingly, protein levels of several P-450 forms are elevated in rat liver following hypophysectomy [P-450 forms designated 2a (gene IIIA2), RLM2 (gene IIA2), and PB-4 (gene IIB1)], whereas protein levels of others are suppressed [e.g., P-450 2c (gene IIC11)]. In the present study, microsomal steroid hydroxylase activities associated with these same P-450 forms were found to be decreased by hypophysectomy, despite elevations in protein levels for several of them. Studies were, therefore, undertaken to determine the biochemical basis for this decrease in microsomal P-450 enzyme specific activity. In vivo treatment of hypophysectomized rats with gonadotropin, under conditions that restore heme to testis P-450, and heme reconstitution experiments carried out with liver homogenates indicated that a deficiency in P-450-associated heme is unlikely to account for the observed decreases in liver P-450 enzyme specific activity. Analysis of the flavoprotein P-450 reductase, however, revealed that the reductase protein and its associated cytochrome c reductase activity are decreased by 50 to 75% in liver microsomes isolated from hypophysectomized rats. Moreover, supplementation of isolated liver microsomes with exogenous purified P-450 reductase stimulated microsomal steroid hydroxylase activity preferentially in the hypophysectomized rats, to levels consistent with the observed changes in P-450 protein levels. Thus, a deficiency in P-450 reductase, which is a rate-limiting component for many P-450-dependent hydroxylation reactions, appears to be responsible for the decrease in steroid hydroxylase specific activity in the hypophysectomized rats. Although growth hormone, adrenocorticotropic hormone, and chorionic gonadotropin were each ineffective at restoring hepatic P-450 reductase when administered to hypophysectomized rats, substantial restoration of P-450 reductase levels could be achieved by treatment of the hypophysectomized rats with thyroxine. Thyroxine treatment of these rats also elevated the microsomal steroid hydroxylase activities associated with the individual hepatic P-450 forms to levels commensurate with their respective P-450 protein levels. These results establish that hepatic P-450 reductase is subject to hormonal controls that are distinct from those governing cytochrome P-450 expression and further demonstrate the complexity of endocrine control of hepatic steroid hormone metabolism.

Human growth hormone treatment of hypophysectomized rats increases the proportion of type-1 fibres in skeletal muscle

Abstract: The studies describe alterations after hypophysectomy in the proportion of the type-1 and type-2 fibres in rat skeletal muscles, and the effects of replacement treatment with pituitary human (h) GH. Cytochemical analysis of myosin ATPase, succinate dehydrogenase and lactate dehydrogenase activities in sections of rat hind limb muscles were used as markers of fibre type and revealed that hypophysectomy reduced the proportion of type-1 fibres by 50% in soleus and in extensor digitorum longus muscles. This reduction in the proportion of type-1 fibres was accompanied by the appearance of transitional fibres (type 2C/1B). Following seven daily injections of hGH (60 mIU/day) to hypophysectomized rats, the proportion of type-1 fibres in both soleus and in extensor digitorum longus was increased with a concomitant reduction in the number of transitional fibres. After 11 days of treatment, all these transitional fibres had reverted back to type-1 fibres. Only hGH was observed to elicit this effect; injections of other pituitary hormones had no effect on the proportions of these transitional fibres. These alterations in fibre type occurred more rapidly than the changes reported after prolonged electrical stimulation of muscle or following extended exercise. These findings suggest that hypophysectomy and GH injection can result in a rapid alteration in the fibre composition of skeletal muscle, which may have important implications in terms of the resistance to fatigue and speed of contraction of the muscle.

MR Imaging of the ectopic bright signal of posterior pituitary regeneration

Abstract: High-field-strength MR studies of 13 patients with sellar and/or parasellar tumors revealed an aberrant location of the posterior pituitary bright signal in the hypothalamus in seven cases and in relation to the pituitary infundibulum in six cases. Five of the MR studies were obtained in patients who had not had surgery and had pituitary adenomas producing compression and/or destruction of the posterior lobe. In the other eight cases, the aberrant bright signal occurred after hypophysectomy in seven patients and after removal of a craniopharyngioma in the eighth. Accumulation of neurosecretory material and regeneration of pituitary tissue in these ectopic locations have been documented previously in animal experiments and in a few reports in humans after hypophysectomy. MR imaging now provides further corroborative evidence in vivo of this process in which a "miniature posterior lobe" is formed.

Hypophysectomy of the Fetal Lamb Leads to a Fall in the Plasma Concentration of Insulin-Like Growth Factor I (IGF-I), but not IGF-II

Abstract: The role of the pituitary gland in the regulation of the plasma concentrations of insulin-like growth factors (IGFs) in the late gestation sheep fetus has been examined. Singleton sheep fetuses were either hypophysectomized or shamoperated between days 110-120 of gestation. Blood samples were then collected via carotid cannulae at least three times weekly for the remainder of gestation. In some hypophysectomized fetuses T4 was administered (100 g/day) to overcome the hypothyroidism caused by hypophysectomy. Blood samples were also obtained from lambs during the perinatal period, neonatal lambs within 1-10 days after birth, and pregnant and nonpregnant adult ewes. All plasma samples were subjected to Sephadex G- 50 gel filtration under acidic conditions (pH 2.3) to eliminate IGF-binding protein activity. The fractions containing the free IGF peptides were collected and assayed for IGF-I by heterologous RIA, and IGF-II by a homologous RRA. Plasma concentrations of IGF-I and IGF-II did not change with advanc...

Regulation of Testicular Inhibin Subunit Messenger Ribonucleic Acid Levels in Vivo: Effects of Hypophysectomy and Selective Follicle-Stimulating Hormone Replacement*

Abstract: To examine the pretranslational regulation of inhibin subunits in the rat testis by FSH, we studied the effects of hypophysectomy with or without selective FSH replacement on testicular inhibin subunit mRNA levels in immature and adult animals. In the first experiment (Exp I), sexually immature (20–23 days old) intact and hypophysectomized male rats were killed 1, 3, and 7 days after surgery, and the testicular content of inhibin subunit mRNAs was determined by filter hybridization. A second group of immature, intact, or hypophysectomized rats was treated with saline or FSH for 7 days as follows: I) intact, saline; II) hypophysectomized, saline; III) hypophysectomized, FSH [0.05 μg/100 g BW, sc, twice daily (BID)]; IV) hypophysectomized, FSH (0.50 μg/100 g BW, sc, BID); V) hypophysectomized, FSH (5.0 μg/100 g BW, sc, BID); and VI) hypophysectomized, FSH (50.0 μg/100 g BW, sc, BID). In the second experiment (Exp II), adult (60 days old) intact or hypophysectomized animals were treated with saline,...

Regulation of hepatic cortisol sulfotransferase in rats by pituitary growth hormone.

Abstract: Cytosolic sulfating activities of 4-pregnen-11 beta, 17 alpha, 21-triol-3,20-dione (cortisol) to the 21-sulfate were 4 to 5 times higher in livers of female than male adult rats. The activity was decreased by administration of testosterone propionate (TP) to ovariectomized, but not to intact, female rats. In male rats, the rate of cortisol sulfation was elevated by neonatal castration and was restored in part by the administration of TP to the castrated rats. In addition, the sulfating activity in adult male rats was increased by the treatment with estradiol benzoate. Hypophysectomy almost completely decreased cytosolic cortisol-sulfating activity in male rats. The activity in hypophysectomized male rats was not increased by the treatment with hydrocortisone, TP, estradiol benzoate, or somatomedin C but was restored by the intermittent injection of human growth hormone (hGH). Further, the continuous infusion of hGH, to mimic the female secretory pattern, increased more efficiently the rate of cortisol sulfation. Hypophysectomy of female rats also decreased, but not completely, the sulfating activity. Treatment of female hypophysectomized rats intermittently with hGH had no appreciable effect, but the continuous infusion increased the activity effectively. The involvement of pituitary growth hormone in the hepatic cortisol sulfation was also supported by the experiment using neonatally glutamate-treated rats and by the observation of developmental changes in the cortisol-sulfating activity. These results indicate that pituitary growth hormone is one of the major factors regulating hepatic levels of cortisol sulfation in rats and that the higher activity in the female than the male is due mainly to the difference in the secretory pattern of growth hormone in the adult animals.

Suppression of hepatic levels of an ethanol-inducible P-450DM/j by growth hormone: relationship between the increased level of P-450DM/j and depletion of growth hormone in diabetes.

Abstract: The mechanism of the suppression of an ethanol-inducible cytochrome P-450 (P-450DM/j) by pituitary hormone has been studied in rats. The hepatic content of P-450DM/j protein quantitated by Western blots was low but was 2-fold higher in male than female untreated rats (75 and 34 pmol/mg of protein, respectively). The content was increased 2.6-fold (male) and 5.6-fold (female) by hypophysectomy and the sex-related difference was abolished. Treatment of hypophysectomized rats with human growth hormone (hGH), but not with prolactin, reversed the increased amounts of P-450DM/j protein. The hGH-induced suppression was more effective with the continuous infusion than intermittent injection. The hepatic level of P-450DM/j mRNA, determined by the use of a 23-mer oligonucleotide probe, was also changed by hypophysectomy and/or hGH-treatment, largely in parallel with the changes in the content of P-450DM/j protein and microsomal p-nitrophenol and aniline hydroxylations. These results suggest that growth hormone exerts the suppressive effect on P-450DM/j through a somatogenic receptor-mediated process. In another growth hormone-depleted condition, diabetes, the hepatic level of P-450DM/j mRNA was also increased to a level similar to that in hypophysectomized rats, but the protein content was 2- to 3-fold higher in diabetic than hypophysectomized rats. These results indicate, in addition to the reduction of serum growth hormone level, the presence of another stimulatory factor, which acts translationally or posttranslationally in livers of diabetic rats. On the other hand, coordinate changes in the level of P-450DM/j protein and the mRNA in hypophysectomized rats indicate that growth hormone acts rather directly and suppresses the level of P-450DM/j mainly at a pretranslational step in rat livers.

Plasma growth hormone pattern and androgens influence the levels of corticosteroid-binding globulin in rat serum.

Abstract: The serum concentration of corticosteroid-binding globulin (CBG) is higher in female rats than in males. Combined hypophysectomy and gonadectomy of female rats reduced the serum concentration of CBG as measured by steady-state polyacrylamide gel electrophoresis, whereas hypophysectomy of male rats increased serum CBG. These effects were seen despite replacement therapy with thyroxine and glucocorticoids. Moreover, neither androgen nor oestrogen treatment affected the serum concentrations of CBG in hypophysectomized rats. Continuous infusions of human or bovine GH (1.4 U/kg per day), by means of osmotic minipumps for 1 week, increased serum concentrations of CBG in both hypophysectomized male and female rats. In contrast, intermittent GH replacement therapy by s.c. injections at 12-h intervals either had no effect or suppressed serum CBG levels. In male rats, neonatal (days 1-2) gonadectomy increased CBG levels more than did prepubertal (day 25) gonadectomy, and testosterone replacement therapy reversed these effects. It is concluded that GH increases the serum CBG levels of hypophysectomized rats when it is given in a continuous manner, but not when given intermittently. The sex difference in serum CBG levels of normal rats may, therefore, be attributed to the more continuous secretory pattern of GH previously observed in female rats.

Role of growth hormone in modulating the constitutive and phenobarbital-induced levels of two P-4506β (testosterone -6βhydroxylase) mRNAs in rat livers

Abstract: The role of growth hormone in the expression of two forms of hepatic cytochrome P-450(P-450), P-450(6)beta-1(6 beta-3), and P-450(6)beta-4, was investigated using RNA blots. The level of P-450(6)beta-1(6 beta-3) mRNA was twenty times higher than that of P-450(6) beta-4 mRNAs in untreated male rat livers. The levels of P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs were increased two fold and three fold, respectively, by hypophysectomy of adult male rats. By intermittent injection of human growth hormone (hGH) into hypophysectomized male rats, both mRNAs were decreased to the level of normal rats, and almost disappeared after continuous infusion of hGH. In female rats, these two mRNAs were not detected, but were increased remarkably by hypophysectomy. The increases in these mRNAs were almost abolished after continuous infusion of hGH in hypophysectomized female rats. The effect of hGH on PB-mediated induction of P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs was also examined. The PB-mediated increases in P-450(6)beta-1(6 beta-3) and P-450(6)beta-4 mRNAs were higher in hypophysectomized male rats (2.5-fold and 10.9-fold, respectively) than in normal male rats (1.5-fold and 5.2-fold, respectively). Thus, the levels of P-450(6)beta-1(6-beta-3) and P-450(6)beta-4 mRNAs were 4.1-fold and 7.3-fold, respectively, higher in PB-induced hypophysectomized rats than in normal male rats. Concerning the postnatal developmental profiles, P-450(6)beta-1(6 beta-3) mRNA was detectable at neonate and reached a maximal level at around 17 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone and testosterone can independently stimulate the growth of hypophysectomized prepubertal lambs without any alteration in circulating concentrations of insulin-like growth factors.

Abstract: Castrated prepubertal lambs were hypophysectomized and then treated with GH and testosterone either alone or in combination over a series of 3-week treatment periods. Hypophysectomy resulted in a rapid reduction in skeletal growth rate which could be reversed by the administration of either GH (4 IU three times a week for 3 weeks) or testosterone propionate (10 mg daily for 3 weeks). When GH or testosterone treatment was withdrawn, skeletal growth fell to the post-operative rate. Combined treatment with both GH and testosterone was no more or less effective than either hormone given singly. The order of administration did not have any effect on the growth rate. Circulating concentrations of insulin-like growth factor-I (IGF-I) were reduced by hypophysectomy, but neither GH nor testosterone treatment, alone or in combination, had any effect on IGF-I concentrations. Concentrations of IGF-II rose following hypophysectomy, and again were not affected by any of the hormonal replacement treatments. In conclusion, both GH and testosterone could stimulate skeletal growth in the hypophysectomized lamb without any alteration of circulating IGF concentrations, and testosterone can clearly stimulate skeletal growth in the complete absence of GH.

Flow cytometric quantification of rat spermatogenic cells after hypophysectomy and gonadotropin treatment.

Abstract: DNA flow cytometry was evaluated as a tool to analyze stage-specific changes that occur in absolute cell numbers in the testes. Hypophysectomy was selected as a model system for perturbing testicular cell types, since the cytological sequelae of this treatment post-hypophysectomy in the rat are well documented in the literature. Rat spermatogenic cells in stages II-V, VII, and IX-XIII of the seminiferous epithelial cycle (as defined by Leblond and Clermont, 1952) were quantified in numbers per standard length of seminiferous tubule by DNA flow cytometry after hypophysectomy and subsequent gonadotropin treatment. In agreement with previous histological studies, we found that acrosome- and maturation-phase spermatids disappeared from the seminiferous epithelium after 17 days post-hypophysectomy, whereas meiosis and early spermiogenesis continued at least 164 days. The number of meiotic cells and round spermatids gradually decreased after hypophysectomy. Changes were observed as early as Day 6 post-hypophysectomy. Treatment with human chorionic gonadotropin (hCG) alone maintained most cell numbers within normal limits, and follicle-stimulating hormone (FSH) was needed in addition to hCG to maintain the normal number of cells with the amount of DNA contained in primary spermatocytes and spermatogonia in G2/M-phase (4C) in stages IX-XIII and elongated spermatids (1C') in stages II-V of the epithelial cycle. The absolute numbers of spermatogenic cells at different phases of maturation provide a useful reference for quantitative studies of spermatogenesis. Pathological changes in the seminiferous epithelium can be detected and quantified by DNA flow cytometry.

Hormonal regulation of peripheral benzodiazepine binding sites in female rat adrenal gland and kidney.

Abstract: The effect of hypophysectomy and hormonal replacement on the density of peripheral benzodiazepine binding sites (PBS) in rat adrenal gland and kidney was studied. In the adrenal gland, hypophysectomy caused a significant decrease of 3-fold in PBS density. In the kidney, in contrast, hypophysectomy did not affect PBS density. In the adrenal gland, adrenocorticotropic hormone (ACTH) administered to hypophysectomized rats caused a significant increase of more than 5-fold in PBS density compared to untreated hypophysectomized rats, and of more than 1.6-fold compared to intact rats. In contrast, the hormones pregnant mare serum gonadotropin (PMSG), diethylstilbestrol (DES), and hydrocortisone (HC), administered to hypophysectomized rats, failed to restore PBS density in the adrenal gland. In the kidney, HC administered to hypophysectomized rats caused an increase of 1.4-fold in PBS density compared to untreated hypophysectomized and intact rats. In contrast, the hormones ACTH, PMSG, and DES, administered to hypophysectomized rats, did not affect PBS density in the kidney. None of the hormones tested altered the equilibrium dissociation constant of PBS in either the adrenal gland or the kidney. These findings indicate that PBS density in rat adrenal gland and kidney is hormonally modulated.

The direct effect of the thyroid hormone on cardiac chronotropism.

Abstract: To establish whether thyroid hormone modifies the heart rate directly or through an action on other neuroendocrine modulators, the authors have examined several animals models differing in the plasma levels of such compounds. Induction of the hypothyroid state in rats produced a slow onset of bradycardia, which may be removed by a prolonged triiodothyronine treatment. The involvement of TSH was excluded as, by comparing thyroidectomized, hypophysectomized and cold exposed rats, the heart rate was found to vary according to the thyroid levels and not to the TSH levels. Moreover growth hormone, corticotropin and gonadotropins do not influence the heart rate, as the bradycardia induced by hypophysectomy was fully removed by triiodothyronine treatment. The lack of influence by ACTH and GnH was confirmed by treatment of thyroidectomized rats with corticosteroids or testosterone, respectively. Finally, thyroid hormone did not act on the heart rate by changing the norepinephrine output at the sympathetic nerve endings in the heart. In fact, thyroidectomy produced a more intense bradycardia than sympathectomy, and such bradycardia was equally removed by triiodothyronine treatment in thyroidectomized rats and in thyroidectomized and then sympathectomized ones. The authors suggest that the direct effect of the thyroid hormone on cardiac chronotropism is due to an early enhancement of beta-adrenoceptors, followed by a late modification of the electrophysiological properties of the myocardium.

Immunoreactive Prolactin in the Hypothalamus and Cerebrospinal Fluid of Male and Female Rats

Abstract: Immunoreactive prolactin (ir-PRL) has been identified in the cerebrospinal fluid (CSF) and brain of the male and female rat. In this study we determined the concentration of ir-PRL in the CSF and hypothalamus under conditions known to increase or decrease serum PRL. Hypophysectomy (60 days) significantly decreased the concentration of ir-PRL in the CSF of male (4.9 ± 0.7 vs. 3.0 ± 0.3 ng/ml) and female (5.8 ± 0.9 vs. 3.1 ± 0.5 ng/ml) rats. However, the effect of long-term hypophysectomy on hypothalamic ir-PRL was gender-dependent. That is, in the male rat hypophysectomy did not affect the content of ir-PRL in the median eminence, ventral hypothalamus or dorsal hypothalamus. In contrast, in the female rat, long-term hypophysectomy decreased the content of ir-PRL in the median eminence, ventral hypothalamus, and dorsal hypothalamus 37, 40, and 47%, respectively. Estradiol replacement to the hypophysectomized female rat normalized the content of ir-PRL in the median eminence (96 ± 5.8 to 131 ± 9.6 ng/mg protein), ventral hypothalamus (11 ± 0.6 to 16.0 ± 1.1 ng/mg protein), dorsal hypothalamus (4.7 ± 0.4 to 8.6 ± 0.4 ng/mg protein), and the concentration ir-PRL in the CSF (2.5 ± 0.3 to 4.6 ± 0.4 ng/ml). In intact female rats, administration ofhaloperidol induced a marked hyperprolactinemia, and significantly increased CSF ir-PRL (5.1 ± 1.5 vs. 18.0 ± 3.8 ng/ml). However, in the same rats, the content of ir-PRL in the median eminence was significantly decreased while the ir-PRL content in the ventral hypothalamus and dorsal hypothalamus was unaffected. Administration of haloperidol to hypophysectomized female rats did not affect the concentration of ir-PRL in the CSF, but decreased the content of ir-PRL in the median eminence (83.0 ± 7.3 to 62.6 ± 6.8 ng/mg protein). The detection of ir-PRL in the CSF of hypophysectomized male and female rats indicates that CSF ir-PRL is not completely dependent on plasma ir-PRL. The increase in CSF and hypothalamic ir-PRL in estradiol-, but not haloperidol-, treated hypophysectomized female rats indicates that hypothalamic and CSF ir-PRL is regulated by an estrogen-dependent mechanism at an extrapituitary site. In addition, the failure of hypothalamic ir-PRL to parallel changes in either plasma or CSF ir-PRL indicates that hypothalamic ir-PRL is not derived from the plasma or CSF. In contrast, this study suggests that hypothalamic ir-PRL may be one source of CSF PRL.

Castration induces luteinizing hormone (LH) secretion in hypophysectomized pituitary-grafted rats receiving pulsatile LH-releasing hormone infusions.

Abstract: An in vivo isolated pituitary paradigm was used to examine the extent to which negative feedback actions of testicular hormones are exerted directly at the level of the anterior pituitary gland. Hypophysectomized male rats received single anterior pituitary transplants under the kidney capsule. On the next day each hypophysectomized, graft-bearing (H/G) animal was fitted with a concentric atrial catheter system which allowed for intermittent infusions of LHRH (250 ng/5 min.h) and chronic blood sampling. On the fifth or sixth day of infusions, blood samples were obtained 2 h before sham-castration (n = 6) or castration (n = 5) and at every 2-h interval for 24 h thereafter. For comparison, blood samples were similarly obtained from a group of normal pituitary-intact male rats before and after sham-castration (n = 5) or castration (n = 5). Plasma LH and PRL levels in all animals were determined by RIA. In the H/G sham-castrate rats, LH levels remained constant throughout the 24-h postsurgery period. By contrast, plasma LH concentrations in the H/G castrate rats increased steadily for 18 h, reaching a plateau at levels 2- to 3-fold higher than pretreatment values. The absolute amounts of immunoreactive LH, and the trajectory of the LH rise in the H/G castrates closely resembled those in the normal castrates during the initial 20 h after castration; at subsequent time points, however, these similarities were not apparent, as LH levels in normal castrates continued to rise, while those in H/G castrates did not. PRL levels were not significantly different in H/G rats compared to those in their pituitary-intact counterparts. We conclude from these studies that most of the acute (less than 20 h) effects of castration on LH secretion can be accounted for by pituitary escape from direct negative feedback suppression. At longer times after orchidectomy, however, the continued postcastration rise in LH secretion may increasingly depend upon additional hypothalamic input. It is hypothesized that this added input consists of an acceleration of LHRH pulse frequency.

Muscle regeneration. The effect of hypophysectomy on cell proliferation and expression of insulin-like growth factor-I.

Abstract: Against the background of the importance of growth hormone (GH) for normal muscle growth, a study was performed to investigate whether lack of GH after hypophysectomy affects the cell proliferation and the local production of insulin-like growth factor-I (IGF-I) in the early stages of muscle regeneration in adult rats. The level of IGF-I in the serum of hypophysectomised rats was reduced to about 30% of that of controls. The incorporation of [methyl-3H]thymidine into the regenerating muscle showed a peak 6 days after the operation and then gradually declined to the end of the period of study 30 days after initiation of regeneration by ischemic necrosis. The DNA content rose to a maximum level after 6-8 days, and remained high after 30 days. There was no major difference in the incorporation of [3H]thymidine in regenerating muscle of hypophysectomised and control rats, but the DNA concentration in the regenerating muscles of hypophysectomised rats was significantly reduced after 30 days. There was a corresponding reduction in the number of nuclei per muscle fibre, indicating that hypophysectomy has a small effect on the cell proliferation during the early stages of muscle regeneration. Immunohistochemical demonstration of IGF-I in the regenerating muscle revealed the transient presence of immunoreactive material in satellite cells and myotubes after 6 to 8 days of regeneration but no immunoreactivity after 30 days. No obvious difference was observed between hypophysectomised and control rats, indicating that the endogenous production of IGF-I in regenerating skeletal muscle can occur independently of GH.

Effects of Hypophysectomy and the Insulin-Like and Anti-Insulin Pituitary Peptides on Carbohydrate Metabolism in Yellow Avy/A (BALB/c × VY)F1 Hybrid Mice

Abstract: The amino-terminal portion of human growth hormone, residues 1–43 (hGH1–43), has insulin-potentiating action, while a hyperglycemic pituitary peptide (HP), which co-purifies with human grow...

A comparison of growth regulation of mammalian with amphibian lens epithelium

Abstract: In frogs hypophysectomy causes cell proliferation in lens epithelium to subside entirely, with better than 95% of the cells arresting in G1. The phenomenon has been traced to the action of insulin-like growth factors (IGFs) whose synthesis depends on anterior pituitary hormones, most notably GH. Both GH and purified somatomedin C can reinitiate mitosis in the lenses of hypophysectomized frogs. The present studies were done to determine if growth of rat lenses is controlled as is that of amphibia. It appears this may not be so because hypophysectomy has no effect on division in the rodent system. Protein calorie malnutrition (PCM) reduced the mitotic index and this effect is much enhanced by pituitary ablation. Of interest too, were the observations that the glucocorticoid, dexamethansone, is inhibitory in frog; the effect in rat is uncertain. Injection of bovine pituitary powder has no influence on rat while stimulating the amphibian material. It is therefore possible to modify growth of rat lens epithelium in vivo but the regulating mechanism(s) appears to be distinct from that operating in frogs. Whether the difference(s) is inherent in the cells themselves or is to be sought in the access routes through which they are reached by blood borne factors (e.g. permeability of blood-aqueous barriers) is, at present, unclear.

Secretion of melanocyte-stimulating hormone and adrenocorticotropin from transplanted pituitary pars intermedia in stressed and nonstressed rats.

Abstract: Rats bearing kidney grafts of the pituitary pars intermedia were divided into three groups: unstressed, acutely stressed, and chronically stressed. Corresponding sham-operated rats were used for comparisons. Twenty days after grafting, the rats were sacrificed and alpha-melanocyte-stimulating hormone (alpha-MSH), adrenocorticotropin (ACTH), and corticosterone were estimated in plasma. The adrenal/body weight ratio and DNA content of the glands were also investigated. The following results were obtained: MSH was found not to be increased in unstressed rats, but it was in grafted animals subjected to acute and chronic swimming stress. ACTH and corticosterone rose in all three groups. Adrenal/body weight ratio and DNA content increased only in grafted chronically stressed rats. Moreover, plasma corticosterone was found higher in grafted hypophysectomized rats than in non-grafted hypophysectomized animals. Administration of ergocryptine to nonstressed grafted rats induced a decrease in the blood content of ACTH and MSH, indicating that the grafts were the source of a part of the circulating ACTH. On the other hand, the fall in MSH levels could show the effect of the drug upon the pars intermedia. Comparison of the ratios of both hormones released in incubations showed that grafts secreted more ACTH than MSH; on the other hand, when intact neurointermediate lobes were incubated, MSH predominated over ACTH. For the first time it is demonstrated that the pars intermedia can secrete ACTH in vivo. Nevertheless, the ability to secrete this hormone is not a property of normal intact pars intermedia, but it manifests in the transplantations probably due to the overactivity of light cells induced by chronic stoppage of dopaminergic inhibition.